The mechanism of H-2-linked resistance to leukemia development by the radiation leukemia virus variants (A/D-RadLV) has been investigated. Kinetic studies concerned with the expression of H-2D and H-2K class I antigens on RadLV induced preleukemic and leukemic thymocytes have revealed an increase in both products irrespective of resistance or sensitivity to leukemia development. H-2-linked resistance has been shown to be associated with preleukemic cell arrest (preleukemic cells being qualitatively different from autonomous leukemic cells). Preleukemia lymphocytes seem to have an important role in the induction of antileukemia immunity, which is not (or less efficiently) induced by autonomous leukemia cells. Preliminary experiments suggest that dependent preleukemic cells (occurring usually among bone marrow cells of resistant haplotypes) have the characteristics of prothymocytes (theta-; PNA+; TL1,2,4+) whereas autonomous transformed cells (occurring usually among thymocytes of sensitive haplotypes) are mostly theta-positive cells (theta+; PNA-; TL1,2,4-). Thus, the H-2 complex may be involved in target cell selection by RadLV variants, and resistance may be the result of interactions between different H-2-controlled immune mechanisms.